Abstract: In order to further improve the processing performance of CNC machine, the static and dynamic characteristics of the spindle box of the vertical machining center actually designed and produced by an enterprise is analyzed in this paper firstly. Secondly, according to the results of finite element analysis, the original structure of the spindle box is optimized. The dynamic stiffness and mass of the spindle box is taken as the objective, and optimization of the size and position of the stiffeners is carried out by using the response surface method. Finally, the static and dynamic analysis on the optimized spindle box structure is performed again to verify whether the mechanical structural rigidity is strengthened. The analysis results show that the mechanical structure stiffness of the optimized headstock is slightly improved, which indicates that the initial structural design of the headstock is reasonable. The method of correlation analysis in this paper would lay a theoretical foundation for the actual production and provide technical support for the similar product development of the related enterprises.